Increased incidence of post-operative respiratory failure in patients with pre-operative SARS-CoV-2 infection.

OBJECTIVE: While studies have reported increased post-operative pulmonary complications with SARS-CoV-2 infection, many are limited by use of historical controls or focus on less severe respiratory complications. We characterized the association between pre-operative SARS-CoV-2 infection and post-operative respiratory failure (PORF). DESIGN AND SETTING: This was a single center retrospective cohort study in New York City between March 14-June 14, 2020. PATIENTS: Exclusion criteria were age < 18-years, obstetric procedures, absence of SARS-CoV-2 PCR testing, and pre-operative respiratory failure. A total of 778 patients met criteria, of which 87 had SARS-CoV-2. MEASUREMENTS: The primary outcome, PORF, included inability to extubate for ≥24 h or unplanned re-intubation within 5 days. Multiple exposures were measured including SARS-CoV-2 infection 4 weeks before or 5 days after surgery. Multivariable logistic regression was performed to adjust for pre-operative hypoxemia, oxygen use, and pneumonia as well as tachycardia, gender, Charlson Comorbidity Index (CCI), Surgical Mortality Probability Model (S-MPM) index, and peri-operative blood transfusion. MAIN RESULTS: SARS-CoV patients had higher CCI (P = 0.007) and S-MPM scores (P = 0.02). The incidence of PORF was 16% versus 7% in uninfected comparators (P = 0.001). Amongst infected individuals, 39% exhibited symptoms of COVID-19 and PORF was more common in these patients compared to asymptomatic individuals (26% vs. 9%, P = 0.04). Adjusted analysis revealed increased odds of PORF with infection (OR 2.8, 95% CI 1.2-6.2). This persisted even when adjusting for probable mediators such as pre-operative hypoxemia. Infected patients also demonstrated increased adjusted odds of 30-day mortality (OR 3.5, 95% CI 1.4-9.1). CONCLUSIONS: Detection of SARS-CoV-2 infection within 4 weeks before or 5 days after surgery is associated with increased odds of 5-day PORF and 30-day mortality. This supports delaying elective surgery, but questions remain regarding the applicability of this recommendation for asymptomatic patients needing urgent or semi-urgent procedures such as oncologic surgery.

Maternal Choline Supplementation Modulates Placental Markers of Inflammation, Angiogenesis, and Apoptosis in a Mouse Model of Placental Insufficiency.

Dlx3 (distal-less homeobox 3) haploinsufficiency in mice has been shown to result in restricted fetal growth and placental defects. We previously showed that maternal choline supplementation (4X versus 1X choline) in the Dlx3+/- mouse increased fetal and placental growth in mid-gestation. The current study sought to test the hypothesis that prenatal choline would modulate indicators of placenta function and development. Pregnant Dlx3+/- mice consuming 1X (control), 2X, or 4X choline from conception were sacrificed at embryonic (E) days E10.5, E12.5, E15.5, and E18.5, and placentas and embryos were harvested. Data were analyzed separately for each gestational day controlling for litter size, fetal genotype (except for models including only +/- pups), and fetal sex (except when data were stratified by this variable). 4X choline tended to increase (p < 0.1) placental labyrinth size at E10.5 and decrease (p < 0.05) placental apoptosis at E12.5. Choline supplementation decreased (p < 0.05) expression of pro-angiogenic genes Eng (E10.5, E12.5, and E15.5), and Vegf (E12.5, E15.5); and pro-inflammatory genes Il1b (at E15.5 and 18.5), Tnfα (at E12.5) and Nfκb (at E15.5) in a fetal sex-dependent manner. These findings provide support for a modulatory effect of maternal choline supplementation on biomarkers of placental function and development in a mouse model of placental insufficiency.